دورية أكاديمية
Bidirectional effects of corticosterone on splenic T-cell activation: critical role of cell density and culture time.
العنوان: | Bidirectional effects of corticosterone on splenic T-cell activation: critical role of cell density and culture time. |
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المؤلفون: | Wiegers GJ; Max Planck Institute of Psychiatry, Section of Neuropsychopharmacology, Munich, Germany., Stec IE, Klinkert WE, Linthorst AC, Reul JM |
المصدر: | Neuroendocrinology [Neuroendocrinology] 2001 Feb; Vol. 73 (2), pp. 139-48. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Karger Country of Publication: Switzerland NLM ID: 0035665 Publication Model: Print Cited Medium: Print ISSN: 0028-3835 (Print) Linking ISSN: 00283835 NLM ISO Abbreviation: Neuroendocrinology Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basel : Karger Original Publication: Basel. |
مواضيع طبية MeSH: | Corticosterone/*pharmacology , Lymphocyte Activation/*drug effects , Spleen/*cytology , T-Lymphocytes/*drug effects , T-Lymphocytes/*immunology, Animals ; Antibodies, Monoclonal/pharmacology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; Cell Count ; Cells, Cultured ; Concanavalin A/pharmacology ; Corticosterone/administration & dosage ; Dose-Response Relationship, Drug ; Male ; Rats ; Rats, Wistar ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Time Factors |
مستخلص: | Glucocorticoids inhibit stimulus-induced T-cell proliferation, an early and essential parameter of cellular immunity. It was recently found however that physiological concentrations of glucocorticoids can also accelerate, not only inhibit, rat T-cell mitogenesis. We investigated mechanism(s) underlying mitogenic actions of glucocorticoids on anti-T-cell receptor (TCR)- and concanavalin A (Con A)-induced T-cell proliferation. Surprisingly, the ability of the glucocorticoid corticosterone (CORT) to either enhance or inhibit T-cell proliferation was found to depend primarily on the cell density and the timing of the cultures. At cell densities up to 1 x 10(5) cells/well (i.e. 'low' density), CORT inhibited T-cell proliferation irrespective of the culture time. In contrast, at cell densities of 2 x 10(5) cells/well and higher ('high' density), CORT potently stimulated T-cell mitogenesis during the first 2-3 culture days, but subsequently inhibited the proliferative response after 5-7 days. The glucocorticoid receptor antagonist RU486 completely abolished the effects of CORT. However, production of the main T cell growth factor interleukin (IL)-2 was inhibited by CORT at both 'low' and 'high' cell densities. In addition, irrespective of cell density, T-cell mitogenesis under either control conditions or in presence of CORT was completely blocked by an anti-IL-2-receptor-alpha-chain (IL-2Ralpha) antibody, indicating that T-cell proliferation was dependent on the IL-2 pathway. Immunofluorescence staining of IL-2Ralpha on CD4+ cells after 2-3 days in culture was increased by CORT, but only on cells cultured at 'high' density. Thus, glucocorticoids increase T-cell responsiveness to IL-2 under conditions of 'high' cell density only. We conclude that glucocorticoids may contribute to a more efficient early stage of cellular immune responses under conditions of intimate cell-to-cell contact (i.e. 'high' cell density), a situation likely to be present in vivo, for instance in lymph nodes. Thus, these findings are relevant to our understanding of the glucocorticoid control of immune function. (Copyright 2001 S. Karger AG, Basel.) |
المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Receptors, Antigen, T-Cell) 0 (Receptors, Antigen, T-Cell, alpha-beta) 11028-71-0 (Concanavalin A) W980KJ009P (Corticosterone) |
تواريخ الأحداث: | Date Created: 20010313 Date Completed: 20010510 Latest Revision: 20171101 |
رمز التحديث: | 20231215 |
DOI: | 10.1159/000054630 |
PMID: | 11244301 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0028-3835 |
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DOI: | 10.1159/000054630 |